A regulatory code for neurogenic gene expression in the Drosophila embryo

Bioinformatics methods have identified enhancers that mediate restricted expression in the Drosophila embryo. However, only a small fraction of the predicted enhancers actually work when tested in vivo. In the present study, co-regulated neurogenic enhancers that are activated by intermediate levels of the Dorsal regulatory gradient are shown to contain several shared sequence motifs. These motifs permitted the identification of new neurogenic enhancers with high precision: five out of seven predicted enhancers direct restricted expression within ventral regions of the neurogenic ectoderm. Mutations in some of the shared motifs disrupt enhancer function, and evidence is presented that the Twist and Su(H) regulatory proteins are essential for the specification of the ventral neurogenic ectoderm prior to gastrulation. The regulatory model of neurogenic gene expression defined in this study permitted the identification of a neurogenic enhancer in the distant Anopheles genome. We discuss the prospects for deciphering regulatory codes that link primary DNA sequence information with predicted patterns of gene expression

Compromised fidelity of B-cell tolerance checkpoints in AChR and MuSK myasthenia gravis

Myasthenia gravis () is an autoimmune condition in which neurotransmission is impaired by binding of autoantibodies to acetylcholine receptors (hR) or, in a minority of patients, to muscle specific kinase (Mu). There are differences in the dominant IgG subclass, pathogenic mechanisms, and treatment responses between the two subtypes (hR or Mu). The antibodies are thought to be T-cell dependent, but the mechanisms underlying their production are not well understood. One aspect not previously described is whether defects in central and peripheral tolerance checkpoints, which allow autoreactive B cells to accumulate in the naive repertoire, are found in both or either form of . An established set of assays that measure the frequency of both polyreactive and autoreactive B cell receptors () in naive populations was applied to specimens collected from patients with either hR or Mu and healthy controls. Radioimmuno- and cell-based assays were used to measure binding to hR and Mu. The frequency of polyreactive and autoreactive s (n = 262) was higher in both hR and Mu patients than in healthy controls. None of the -derived s bound hR or Mu. The results indicate that both these subtypes harbor defects in central and peripheral B cell tolerance checkpoints. Defective B cell tolerance may represent a fundamental contributor to autoimmunity in and is of particular importance when considering the durability of myasthenia gravis treatment strategies, particularly biologics that eliminate B cells

Design tool for thermal energy storage in buildings

The requirements on reducing the energy use and peak heating and cooling power in building applications is now in focus in many countries. Thermal Energy Storage (TES) technology has been meticulously studied during the past decades due to its benefits in terms of higher energy storage density per unit volume, as well as given and a narrow temperature operation range [Nazir et al., 2019]. However, the lack of full scale application of TES in building industry shows a need for development of easily accessible guidelines and validated design tools, for such technology to be promoted by designers, decision makers and researchers [Castel et Sol\ue9, 2015].This limitation is addressed here by proposing a novel numerical design tool for TES in Building Applications. The tool, developed under MATLAB/GUI environment, is based on a physically sound TES model [Stathopoulos et al., 2017, 2016], providing a database with commercially available Phase Change Materials (PCM). The tool uses input from the potential user (type of application, energy demand, operating condition, etc…) to select suitable PCMs and calculate the dimensions of the proposed system and its operation profile (temperature, power and energy variation). Results are then presented in a separate file, summarizing the information provided by the user, the selected PCMs including their properties and the performance of the system.The tool is targeted to designers, decision makers and researchers for increased possibilities for TES design in building district energy systems

Proteomics of Aqueous Humor as a Source of Disease Biomarkers in Retinoblastoma

Aqueous humor (AH) can be easily and safely used to evaluate disease-specific biomarkers in ocular disease. The aim of this study was to identify specific proteins biomarkers in the AH of retinoblastoma (RB) patients at various stages of the disease. We analyzed the proteome of 53 AH samples using high-resolution mass spectrometry. We grouped the samples according to active vitreous seeding (Group 1), active aqueous seeding (Group 2), naive RB (group 3), inactive RB (group 4), and congenital cataracts as the control (Group 5). We found a total of 889 proteins in all samples. Comparative parametric analyses among the different groups revealed three additional proteins expressed in the RB groups that were not expressed in the control group. These were histone H2B type 2-E (HISTH2B2E), InaD-like protein (PATJ), and ubiquitin conjugating enzyme E2 V1 (UBE2V1). Upon processing the data of our study with the OpenTarget Tool software, we found that glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and CD44 were more highly expressed in the RB groups. Our results provide a proteome database regarding AH related to RB disease that may be used as a source of biomarkers. Further prospective studies should validate our finding in a large cohort of RB patients

Treatment of Bing--Neel syndrome with first line sequential chemoimmunotherapy: A case report

RATIONALE: Bing-Neel syndrome (BNS) is a rare manifestation of Waldenström macroglobulinemia (WM) with <200 cases reported in the literature. Herein, we describe a case of newly diagnosed BNS treated with a novel therapeutic strategy. PATIENT CONCERNS: A 67-year-old woman diagnosed with asymptomatic WM 3 years ago presented with gradual vision deterioration the past 3 months. Ophthalmologic examination revealed bilateral reduction in visual acuity (7/10) and bilateral optic disc swelling which was more prominent in the left eye. DIAGNOSES: Brain imaging revealed bilateral swelling of optic nerves extending from the retina to the optic chiasm and swelling of the left optic tract. Patchy enhancement of optic nerves was also shown upon intravenous contrast administration. Flow cytometry of the cerebrospinal fluid (CSF) revealed the presence of κ-light chain restricted, monoclonal B-lymphocytes. CSF protein electrophoresis showed a monoclonal band in the gamma region and immunofixation was positive for immunoglobulin M and kappa light chain. Thus, the diagnosis of BNS was established. INTERVENTIONS: The patient was initially treated with intrathecal methotrexate and systemic chemotherapy. Following 2 intrathecal methotrexate infusions, CSF flow cytometry did not detect any cells, whereas the patient reported improvement in visual acuity. Therefore, we opted to start maintenance treatment with IV rituximab and per os ibrutinib. OUTCOMES: Following 1 year posttreatment initiation, visual problems have resolved completely and the patient remains on hematologic and imaging complete response. LESSONS: We propose a novel sequential chemoimmunotherapy approach for BNS treatment aiming both at rapid disease control and deep and durable remission with minimization of induced toxicity

BRevê: uma metodologia objetiva de cálculo de emissões para a frota brasileira de veículos

Nos últimos anos, a preocupação com o aumento das emissões de poluentes por veículos automotores tem aumentado. No Brasil há diversas regulamentações no sentido de controlar essas emissões. A quantificação dos poluentes emitidos, além de ser um instrumento de gestão ambiental, também é item necessário para atender à legislação. No Brasil, o Ministério do Meio Ambiente fez um levantamento geral das emissões veiculares e como resultado apresentou, no início de 2011, o Primeiro Inventário Nacional de Emissões Atmosféricas por Veículos Automotores Rodoviários. Nesse inventário são apresentados fatores de emissão para diferentes poluentes, combustíveis, e categorias de veículos. Com base nesses fatores, e tendo como objetivo facilitar o cálculo das emissões de poluentes por veículos automotores, neste trabalho é apresentada uma metodologia (simplificada) e um programa de computador (BRevê.py) capaz de calcular as emissões veiculares de frotas brasileiras de veículos. O programa apresentado possui código aberto e livre e pode ser solicitado aos autores via e-mail. Para demonstrar a facilidade de aplicação do programa desenvolvido, um exemplo simplificado, bem como seus resultados, são apresentados

Compromised fidelity of B-cell tolerance checkpoints in AChR and MuSK myasthenia gravis

Myasthenia gravis () is an autoimmune condition in which neurotransmission is impaired by binding of autoantibodies to acetylcholine receptors (hR) or, in a minority of patients, to muscle specific kinase (Mu). There are differences in the dominant IgG subclass, pathogenic mechanisms, and treatment responses between the two subtypes (hR or Mu). The antibodies are thought to be T-cell dependent, but the mechanisms underlying their production are not well understood. One aspect not previously described is whether defects in central and peripheral tolerance checkpoints, which allow autoreactive B cells to accumulate in the naive repertoire, are found in both or either form of . An established set of assays that measure the frequency of both polyreactive and autoreactive B cell receptors () in naive populations was applied to specimens collected from patients with either hR or Mu and healthy controls. Radioimmuno- and cell-based assays were used to measure binding to hR and Mu. The frequency of polyreactive and autoreactive s (n = 262) was higher in both hR and Mu patients than in healthy controls. None of the -derived s bound hR or Mu. The results indicate that both these subtypes harbor defects in central and peripheral B cell tolerance checkpoints. Defective B cell tolerance may represent a fundamental contributor to autoimmunity in and is of particular importance when considering the durability of myasthenia gravis treatment strategies, particularly biologics that eliminate B cells